The Body Scientific

By Richard Kessin

What have the scientific, pharmaceutical and medical communities done to stifle SARS-CoV-2 infections? There are currently 18 advanced trials of different vaccines, 64 possible new treatments and 23 potential or approved antiviral drugs.

The mRNA vaccines from Pfizer and Moderna provide robust protection, but they are expensive and need to be shipped frozen. Lower-income countries require an effective vaccine that is inexpensive, survives at higher temperature and can be made locally. Corbevax, created at the Baylor College of Medicine, fits these criteria and is currently being made in hundreds of millions of doses in India. Other vaccines (Novovax) produce antibodies to viral proteins in addition to the Spike protein. The Novovax vaccine contains no genetic material.

Beyond vaccines, there are 64 new treatments in development that block or slow infection or some of its consequences, like inflammation. Inflammation makes blood vessels leaky; defensive cells, which rush to the site of infection, squeeze out of the circulatory system and infiltrate the lungs. They fill air sacs with dead neutrophils, eosinophils and fluid, making the patient struggle to breathe. In addition, when these cells die, they release digestive enzymes that can do terrible damage to the lungs or other infected tissues.

The use of steroids to inhibit inflammation was a critical early discovery. According to a review I read recently, it is still the best early intervention. Most viruses have the means to inhibit a host’s immune system: some inhibit interferon synthesis, a critical mobilizer of the immune response; SARS-CoV-2 inhibits the production of natural killer (NK) cells, which recognize infected lung cells and kill them. The more we know about these mechanisms, the better off we will be.

There are currently 23 antivirals approved or in testing, including Merck’s Molnupiravir and Pfizer’s Paxlovid, but others have Emergency Use Authorization as well. Paxlovid, if taken within five days of the onset of symptoms, blocks disease progression and keeps 90 percent of patients from hospitalization. Vaccinated and boosted people usually have a short illness unless they have other complications, and they may not need these therapeutics. But for those who do, or are unvaccinated, the drugs are becoming available in pharmacies.

My friend Jonathan Sanoff keeps track of these things. He told me about a site called the Covid-19 Therapeutics Locator, which the assistant secretary for preparedness and response at the Department of Health and Human Services, Rear Admiral Rachel L. Levine, MD, and her staff have prepared. The site tells potential patients where to find these drugs, whether they are in Puerto Rico or Alaska. The site also includes the number of doses on hand at each site and the total made so far, as well as information on each drug. As new therapies come online, they will appear on the Therapeutics Locator. There are currently seven drugs and monoclonal antibodies on the site. The assistant secretary and her staff do not get much credit, but they should.

 We learned from HIV therapy that an RNA virus can develop resistance to a single drug but cannot evolve resistance to three drugs, which is why it is a pleasant surprise that 23 antivirals have been approved or are in testing. An even better surprise is that some of these drugs inhibit other RNA viruses, including Zika and Ebola.

Nothing in science or medicine must work, no matter how clever the idea. We should not be surprised that 26 vaccines failed, 92 treatments did not pass muster, and 54 antivirals did not inhibit SARS-CoV-2. These results on therapies in the development pipeline have been collected by Heidi Ledford, one of Nature magazine’s senior reporters (Nature, March 3, 2022). I am grateful to her. In that context, the March 11 issue of Science, the flagship publication of the American Academy of Sciences, contains a detailed comparison and analysis of these treatments and ideas on what we need to prepare for the next epidemic. The combination of basic science, private industry and public health services has done well, although praise sounds hollow when millions have died.

What to do? Get vaccinated and boosted. When new boosters designed to attack SARS-CoV-2 or its variants appear, get those too. Even with the vaccine, you may get mild disease, but the name of the game is to prevent progression to serious disease and hospitalization. The new drugs offer reassurance. In places where the virus and infection are in decline, it is time to resume normal life. Or at least that is my plan.